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Simplifying the dental/periodontal management of patients with metabolic bone fragility receiving treatment with denosumab

Denosumab (DNB) is a bone-targeted medication used to preserve structural integrity and minimise the risk of fragility fractures in metastatic cancer and metabolic bone disorders. DNB targets and binds RANK Ligand, inhibiting osteoclast maturation, function, and survival. In contrast with nitrogen-containing bisphosphonates (N-BPs), DNB does not bind to hydroxyapatite and incorporate into bone; thus, bone cellular remodelling recovers rapidly after drug suspension. Denosumab has benn linked to the occurrence of osteonecrosis of the jaw (MRONJ), a uncommon but severe oral side effect with a higher prevalence in metastatic cancer patients than in patients with metabolic bone fragility. Although several oral triggers can initiate MRONJ, invasive oral treatments and tooth extraction still remain the most common precipitating event. In general, tooth extraction and oral surgery should be avoided in patients at increased risk of MRONJ, while extraction of unsalvageable teeth should be performed based on specific risk reduction protocols to eliminate dental/periodontal infections, still protectig from MRONJ onset. Based on the different pharmacological properties of DNB and N-BPs, it is likely that the MRONJ risk profile of patients with metabolic bone fragility receiving receiving different ARs could somewhat vary. We hypothesize the chance to maximize the pharmacokinetic of Prolia\uae and identify a time interval in which invasive oral treatments can ideally take place without restrictions in patients with metabolic bone fragility, provided that careful case selection, adequate communication among specialists, planning of a delayed dosing window and rigorous postoperative follow-up are granted

The dental management of patients at risk of medication-related osteonecrosis of the jaw: New paradigm of primary prevention

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction of antiresorptive and antiangiogenic agents; it is a potentially painful and debilitating condition that can considerably affect the quality of life of patients. Furthermore, even if its epidemiology and pathogenesis have still not been fully clarified, several risk factors related to MRONJ have been recognized in prevention protocols. Three main risk factors are as follows: (i) the type of ONJ-related medications: antiresorptive (e.g., Bisphosphonates, Denosumab) and antiangiogenic drugs (e.g., Bevacizumab, Sunitinib); (ii) the category of patient at MRONJ risk: cancer versus non-cancer patient; (iii) the typologies and timing of dental treatments (e.g., before, during, or after the drug administration). The aim of this paper is to describe the new paradigm by the Italian Society of Oral Pathology and Medicine (SIPMO) on preventive dental management in patients at risk of MRONJ, prior to and during/after the administration of the aforementioned ONJ-related drugs. In reducing the risk of MRONJ, dentists and oral hygienists are key figures in applying a correct protocol of primary prevention for pre-treatment and in-treatment patients. However, the necessity of a multidisciplinary standardized approach, with a sustained dialogue among specialists involved, should be always adopted in order to improve the efficacy of preventive strategies and to ameliorate the patient\u2019s quality of life

Microsurgical reconstruction of the mandible in a patient with evans syndrome: a case report and review of the literature

In this report, we describe the first successful case of microvascular free tissue transfer in a patient with Evans Syndrome (ES), a rare form of idiopathic thrombocytopenic purpura (ITP) and associated autoimmune hemolytic anemia (AIHA). Microvascular surgery in the setting of ES is likely to have higher complication rates because of the increased risk of postoperative bleeding and free flap thrombosis. The case presented here opens up to the feasibility of microvascular reconstruction of patients with coagulation disorders like ES. Every effort should be made to control for hemolytic, thrombocytopenic, and thrombophilic states associated with ES. In the absence of evidence-based treatment guidelines for ES, personalized treatment protocols with high-dose corticosteroids, immunoglobulin, and postoperative anticoagulation regimen are highly recommended

Accuracy of eight-polar bioelectrical impedance analysis for the assessment of total and appendicular body composition in peritoneal dialysis patients

Objective: To establish the accuracy of bioelectrical impedance analysis (BIA) for the assessment of total and appendicular body composition in peritoneal dialysis (PD) patients. Design: Cross-sectional study. Setting: University Nephrology Clinic. Subjects: In all, 20 PD patients and 77 healthy controls matched for gender, age and body mass index. Methods: Whole-body fat-free mass (FFM) and appendicular lean tissue mass (LTM) were measured by dual-energy X-ray absorptiometry. Resistance ( R) of arms, trunk and legs was measured by eight-polar BIA at frequencies of 5, 50, 250 and 500 kHz. Whole-body resistance was calculated as the sum of R of arms, trunk and legs. The resistance index ( RI) was calculated as the ratio between squared height and whole-body or segmental R. Results: RI at 500 kHz was the best predictor of FFM, LTMarm and LTMleg in both PD patients and controls. Equations developed on controls overestimated FFM and LTMarm and underestimated LTMleg when applied to PD patients. Specific equations were thus developed for PD patients. Using these equations, the percent root mean-squared errors of the estimate for PD patients vs controls were 5 vs 6% for FFM, 8 vs 8% for LTMarm and 7 vs 8% for LTMleg. Conclusion: Eight-polar BIA offers accurate estimates of total and appendicular body composition in PD patients, provided that population-specific equations are used

exposure to antiresorptive therapy with bisphosphonates does not induce histological changes in human alveolar jawbone

Aim: The identification of specific alterations in the alveolar jawbone of patients treated with nitrogen-containing bisphosphonates (NBP) but without bisphosphonate-related osteonecrosis of the jaw (BRONJ) may help to identify the early steps of BRONJ and to select patients at risk for it. Materials and Methods: We performed a case-control study. Cases were 60 individuals treated with NBP without clinical and radiological signs of BRONJ and requiring surgical tooth extraction. Controls were 60 individuals never treated with NBP and requiring tooth extraction. Cases and controls were matched by sex (same) and age (within 5 years). 18 categorical (basophile reversal lines, osteoblasts, osteoblastic lines, osteocytes, empty osteocytic lacunae, osteoclasts, Howship's lacunae, vessel dilatation, vascular congestion, arteriolar thickening, intravascular fat globules, calcific fat necrosis, fatty bone marrow, ruptured adipocytes, granular cytoplasm of adipocytes, oil cysts, perivascular fibrosis, diffuse fibrous metaplasia) and 2 ordinal histopathological variables (inflammation and bone maturation) were investigated. Exact univariable and multivariable (correction for gender and age) logistic regression was used to test the association between NBP use and the histopathological variables. Because of multiple comparisons, the critical p-value was set to 0.0025 (0.05/20). Results: Cases and controls did not differ for any study variable except for vascular congestion that was significantly associated with NBP use (multivariable OR = 0.24, exact 95% CI 0.10 to 0.57 for cases vs. controls, p = 0.0006). Conclusions: Use of NBP does not produce specific histological alveolar bone alterations in the absence of overt BRONJ disease

Conservative Surgical Treatment of Bisphosphonate-Related Osteonecrosis of the Jaw with Er,Cr:YSGG Laser and Platelet-Rich Plasma: A Longitudinal Study

Abstract Introduction: The management of bisphosphonate-related osteonecrosis of the jaw (BRONJ), with no evidence-based guidelines, remains controversial. We aimed to evaluate the efficiency of a conservative surgical treatment combining Er,Cr:YSGG laser and platelet-rich plasma (PRP) for the treatment of BRONJ in cancer patients.Methods:We performed a longitudinal cohort study. Inclusion criteria were (1) age 65 18 years; (2) cancer diagnosis; (3) treatment with NBP because of the underlying cancer. Results:We consecutively recruited ten patients diagnosed with BRONJ in stage I or II. These patients underwent a surgical laser-assisted therapy together with autologous PRP. At the latest follow-up at 12 months, clinical improvement was observed in eight patients. Registration Number is IRCT20180329039159N1. Conclusion:We could successfully manage the BRONJ utilizing this combined protocol to heal the 30% of surgically treated sites and to improve the 50% of patients' lesions clinically. Our findings suggest that a surgical approach combined with Er,Cr:YSGG laser and PRP benefit cancer patients with general health issues

Metabolic correlates of subcutaneous and visceral abdominal fat measured by ultrasonography: a comparison with waist circumference

Background: The relative contribution of visceral (VAT) and subcutaneous (SAT) adipose tissue to cardiometabolic disease is controversial. The aim of this study was to evaluate whether dissecting abdominal fat in VAT and SAT using US may detect stronger and more specific association with MS, MS components, hyperuricemia and altered liver enzymes compared to waist circumference. Methods: We performed a cross-sectional study on 2414 subjects aged 18 to 66 years (71 % women) followed at the International Center for the Assessment of Nutritional Status (ICANS, Milan, Italy). VAT and SAT were measured using ultrasonography. Multivariable logistic regression controlling for age and gender was used to evaluate the association of the parameters of interest (waist circumference (WC), VAT, SAT and VAT + SAT) with the MS (international harmonized definition), its components (high triglycerides, low HDL, high blood pressure, high glucose), high uric acid (>= 7 mg/dl), high alanine transaminase (ALT, >= 30 U/l) and high gamma-glutamyl-transferase (GGT, >= 30 U/l). Results: VAT was independently associated with all the outcomes of interest, while SAT was independently associated with MS and only with high blood pressure and high ALT when we considered the single parameters of MS and NAFLD. VAT had the strongest association with high triglycerides, high ALT and high GGT. The VAT + SAT association had the strongest association with MS. WC had the strongest association with low HDL and high blood pressure. VAT and WC were similarly associated to high glucose and high uric acid. Conclusion: US-determined VAT and SAT are both independently associated with MS. Moreover, to our knowledge, we are the first to show that VAT, being associated to all of the MS components in addition to hyperuricemia and altered liver enzymes, performs equally or better than WC except for high blood pressure and low HDL

Association between Serum Atypical Fibroblast Growth Factors 21 and 19 and Pediatric Nonalcoholic Fatty Liver Disease

Atypical fibroblast growth factors (FGF) 21 and 19 play a central role in energy metabolism through the mediation of Klotho coreceptor. Contradictory findings are available about the association of FGF21 and FGF19 with nonalcoholic fatty liver disease (NAFLD) in humans. We investigated the association of serum FGF21, FGF19 and liver Klotho coreceptor with non-alcoholic steatohepatitis (NASH) and fibrosis in children with NAFLD. Serum FGF21 and FGF19 were measured in 84 children with biopsy-proven NAFLD and 23 controls (CTRL). The hepatic expression of Klotho coreceptor was measured in 7 CTRL, 9 patients with NASH (NASH+) and 11 patients without NASH (NASH-). FGF21 and FGF19 showed a tendency to decrease from CTRL (median FGF21 = 196 pg/mL; median FGF19 = 201 pg/mL) to NASH- (FGF21 = 89 pg/mL; FGF19 = 81 pg/mL) to NASH+ patients (FGF21 = 54 pg/mL; FGF19 = 41 pg/mL) (p<0.001 for all comparisons) and were inversely associated with the probability of NASH and fibrosis in children with NAFLD. The hepatic expression of Klotho coreceptor was inversely associated with NASH (R2 = 0.87, p<0.0001) and directly associated with serum FGF21 (R2 = 0.57, p<0.0001) and FGF19 (R2 = 0.67, p<0.0001). In conclusion, serum FGF19 and FGF21 and hepatic Klotho expression are inversely associated with hepatic damage in children with NAFLD and these findings may have important implications for understanding the mechanisms of NAFLD progression. © 2013 Alisi et al